Deferred Cytoreductive Nephrectomy in Unresectable/Metastatic Renal Cell Carcinoma: A Real‐World Multicenter Retrospective Study

OBJECTIVE: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains controversial in the era of modern systemic therapy. We aimed to evaluate the proportion of patients undergoing deferred CN (dCN) and their oncological outcomes in a real-world setting. METHODS: We retrospectively reviewed 651 patients with mRCC who received first-line tyrosine kinase inhibitors (TKIs) or immune-oncology (IO) combinations (nivolumab-ipilimumab or IO-TKI) between 2006 and 2025 at 22 Japanese institutions. Patients with prior nephrectomy or follow-up < 3 months were excluded, leaving 278 eligible patients (TKI 101, IO-TKI 115, Nivo-Ipi 62). Patients were categorized into dCN and non-nephrectomy groups. Outcomes assessed included the proportion of patients undergoing dCN, disease-free survival (DFS), overall survival (OS), and perioperative morbidity. Propensity score-matching and multivariable time-dependent Cox regression were performed. RESULTS: Among 278 patients, 58 (20.9%) underwent dCN (TKI: 24.8%, IO-TKI: 15.7%, and Nivo-Ipi: 24.2%) after a median of 6.6 months of systemic therapy. In the propensity score-matched cohort (n = 58 per group), dCN was significantly associated with improved survival (DFS: HR 0.38; OS: HR 0.19; both p < 0.001). Perioperative complications occurred in 27.6% (grade ≥ 3 in 3.4%) with no grade 4-5 events. Notably, 34.5% were able to discontinue systemic therapy without recurrence, indicating the possibility of durable treatment-free disease control in a subset of patients. CONCLUSIONS: Deferred CN (dCN) was feasible and associated with prolonged survival in selected patients with mRCC. Prospective trials are warranted to confirm its role and refine patient selection.